Type 2 diabetes (T2D) is a chronic disease accompanied by heightened risk for severe health complications such as cardiovascular and peripheral vascular disease, stroke, blindness, and renal failure. The alarming rise in the manifestation of T2D among adolescents and young adults poses an enormous public health burden. Insulin resistance (IR) is a major physiological precursor to T2D. Thus, prevention efforts targeting modifiable risk factors for IR have the potential to diminish the risk of developing T2D significantly. Depressive symptoms often first appear during adolescence, are associated with IR in adolescents and adults, predict adult-onset T2D, and contribute to increased risk for T2D mortality and morbidity, beyond the interrelationship of depression with obesity. The mechanisms underlying the link between depressive symptoms and IR are unclear. Depressive symptoms theoretically induce IR by promoting stress-induced behaviors (altered eating, lowered fitness) and up regulating physiological stress mechanisms (cortisol, neuropeptide Y). Psychotherapy for depression improves IR in adults, but it is uncertain whether ameliorating depressive symptoms prevent progression of IR in adolescents at risk for T2D. The aims of this proposal are: 1) to assess the effects of a 6-wk cognitive-behavioral (CB) depression prevention group vs. a 6-wk standard-of-care health education (HE) group on reducing depressive symptoms and improving IR in adolescent girls at risk for T2D;2) to assess the stress-related behavioral and physiological factors that mediate the relationship underlying decreases in depressive symptoms and improvements in IR;and 3) to pilot delivery of a mindfulness-based stress reduction (MBSR) group to adolescents girls at risk for T2D. The PI, Dr. Lauren Shomaker, is a child clinical psychologist whose background in adolescent development/psychopathology, eating behavior, and pediatric obesity/obesity related health co-morbidities is uniquely suited to advance the aims in this proposal. During the K99 phase, Dr. Shomaker will obtain training to enhance her expertise in: 1) conduct of randomized controlled trials (RCTs) in adolescents, ii) measurement of IR, and iii) assessment of cardiovascular fitness. Dr. Shomaker has assembled a strong mentoring and consultant team with expertise in RCTs for pediatric obesity and IR (Co- Mentors: Marian Tanofsy-Kraff, PhD, Jack Yanovski, MD, PhD), CB depression interventions (Eric Stice, PhD, Marjan Holloway, PhD), cardiovascular fitness (Kong Chen, PhD), stress physiology (Zofia Zukowska, MD, PhD), advanced statistical analysis (Cara Olsen, PhD), and MBSR (Kirk Brown, PhD). The proposed K99/R00 application is the ideal vehicle to promote Dr. Shomaker's ultimate goal of transitioning to an independent career focused upon the interconnections between adolescent psychosocial development and physical health, and the putative mechanisms underlying the links between psychosocial factors and physical well-being. PUBLIC HEALTH RELEVANCE: Type 2 diabetes (T2D) is one of our nation's most common chronic diseases. It affects >7.8% of the U.S., and the societal cost is >$90 billion/yr. In the past, T2D was considered a disease limited to older adults. Yet, there has been an alarming rise in its manifestation among adolescents and young adults. Early onset T2D has been associated with greater risk of end-stage renal disease and death and a shorter life expectancy of 15-27 yrs. Insulin resistance (IR) is a major physiological precursor to T2D. The normative rise in IR that characterizes puberty may render adolescence a sensitive period, triggering the progression of worsening IR among adolescents at risk for T2D. Adolescence also marks a peak period for the onset of elevated depressive symptoms among girls. Elevated depressive symptoms affect over 25% of adolescents. Even in the absence of full criteria for major depressive disorder (MDD), adolescent depressive symptoms are associated with considerable psychosocial and behavioral impairment and a 2-4-fold greater risk of developing MDD. Depressive symptoms also are associated with IR in adolescents and adults and predict T2D onset. Therefore, amelioration of elevated depressive symptoms in adolescent girls who are at risk for T2D has the potential to improve IR and risk for T2D in a considerable subset of youth.